RESUMEN
Background and aims: Pediatric dilated cardiomyopathy (DCM) is a primary cause of heart failure, highlighting the urgent need for effective prognostic markers. Methods: We performed a single-center retrospective study involving 145 children diagnosed with DCM, with a median follow-up period of 4.0 months (interquartile range: 6.2-108.4 months). The relationship between serum uric acid (SUA) levels and all-cause mortality was assessed using Kaplan-Meier survival curves, multivariate Cox proportional hazard models, and restricted cubic spline (RCS) models. Results: Of the 145 children with DCM (median age 5.7 years; 61.4% male), 45 (31%) died within 1 year, and 65 (44.8%) died during the maximum follow-up period. In adjusted multivariate Cox regression models, each log2 SUA increase was linked to a higher risk of 1-year mortality [hazard ratio (HR), 2.66; 95% confidence interval (CI), 1.41-5.01] and overall mortality (HR, 1.97; 95% CI, 1.15-3.37). The highest SUA tertile showed a greater risk of mortality at 1 year (HR, 4.26; 95% CI: 1.5-12.06) and during the maximum follow-up (HR, 2.56; 95% CI: 1.06-6.16) compared with the lowest tertile. RCS models indicated an inverted L-shaped association between baseline SUA levels and overall mortality risk, with age-stratified analyses revealing a linear and U-shaped relationship in children ≤10 and >10 years, respectively. Further age-stratified analyses highlighted the modifying effect of age on this association. Conclusion: Elevated SUA levels are a significant predictor of mortality in pediatric DCM, with a pronounced impact on children under 10 years of age. Therefore, SUA levels could serve as potential biomarkers for risk stratification in this population.
RESUMEN
INTRODUCTION: Coenzyme Q10 (CoQ10) is considered to be beneficial for patients with acute viral myocarditis (AVM). In addition, trimetazidine may be also beneficial to patients with AVM by promoting cardiac energy metabolism. This systematic review and meta-analysis examined the efficacy and safety of combining trimetazidine and CoQ10 with respect to CoQ10 alone in patients suffering from AVM. METHODOLOGY: PubMed, Embase, the Cochrane Library, Wanfang, and China National Knowledge Infrastructure (CNKI) databases were searched for relevant randomized controlled trials (RCTs). An analysis of random effects was employed to combine the results. RESULTS: Sixteen RCTs that included 1,364 patients with AVM contributed to the meta-analysis. Overall, 687 patients received the combined treatment, while 677 received the CoQ10 alone for a duration of 2-12 weeks (mean: 5.2 weeks). In contrast to monotherapy with CoQ10, combined treatment with trimetazidine and CoQ10 significantly improved overall therapy effectiveness (risk ratio [RR]: 1.19, 95% confidence interval [CI]: 1.13 to 1.24, p < 0.001; I2 = 0%). Differences in study parameters such as the incidence of heart failure upon admission, dosage of CoQ10, or length of treatment did not significantly alter the outcomes (p for all subgroup analyses > 0.05). The combined treatment was associated with improved myocardial enzyme levels and recovery of cardiac systolic function as compared to CoQ10 alone (p all < 0.05). In addition, trimetazidine combined with CoQ10 caused no greater increase in adverse events than CoQ10 alone. CONCLUSIONS: Trimetazidine combined with CoQ10 is an effective and safe treatment for AVM.
Asunto(s)
Quimioterapia Combinada , Miocarditis , Trimetazidina , Ubiquinona , Trimetazidina/uso terapéutico , Trimetazidina/administración & dosificación , Humanos , Miocarditis/tratamiento farmacológico , Ubiquinona/análogos & derivados , Ubiquinona/uso terapéutico , Ubiquinona/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Enfermedad AgudaRESUMEN
Pediatric heart failure (HF) is associated with high readmission rates, but the optimal serum potassium range for this population remains unclear. In this single-center retrospective cohort study, 180 pediatric patients hospitalized for HF between January 2016 and January 2022 were stratified into low-potassium (<3.7 mmol/L), middle-potassium (3.7-4.7 mmol/L), and high-potassium (≥4.7 mmol/L) groups based on the distribution of potassium levels in the study population. The primary outcome was readmission for HF within 1 year of discharge. Cox regression and restricted cubic spline models were used to assess the association between potassium levels and 1-year HF readmission rates. Notably, 38.9% of patients underwent 1 or more 1-year readmissions for HF within 1 year. The high-potassium group had a significantly higher readmission frequency than the middle-potassium group. In multivariate Cox regression models, potassium levels of ≥4.7 mmol/L were independently associated with increased 1-year readmission risk. A J-shaped relationship was observed between baseline potassium levels and 1-year readmission risk, with the lowest risk at 4.1 mmol/L. In pediatric patients with HF, a serum potassium level ≥ 4.7 mmol/L was independently associated with increased 1-year readmission risk. Maintaining potassium levels within a narrow range may improve outcomes in this population.
RESUMEN
OBJECTIVE: Persistent pulmonary hypertension of the newborn (PPHN) is one of the critical neonatal diseases associated with high morbidity and mortality. This study attempted to conduct a nomogram prediction model for performing early identification of PPHN and providing effective information for clinical practice. METHODS: A total of 456 newborns who first admitted to the hospital after birth were included in the analysis, including 138 newborns with PPHN and 318 newborns without PPHN (as controls). The optimal predictive variables selection was performed based on LASSO (least absolute shrinkage and selection operator) regression and multivariate logistic regression. Using the selected variables, a nomogram prediction model was developed. To validate the model, the model was assessed using the receiver operating characteristic curve, calibration plot, and clinical impact curve. RESULTS: Six predictors, namely, gestational age, neonatal respiratory distress syndrome, the levels of hemoglobin and creatine kinase-MB, gestational thyroid dysfunction, and Pa o2 , were identified by LASSO and multivariate logistic regression analysis from the original 30 variables studied. The constructed model, using these predictors, exhibited favorable predictive ability for PPHN, with an area under the receiver operating characteristic of 0.897 (sensitivity = 0.876, specificity = 0.785) in the training set and 0.871 (sensitivity = 0.902, specificity = 0.695) in the validation set, and was well calibrated, as indicated by the PHosmer-Lemeshow test values of 0.233 and 0.876 for the training and validation sets, respectively. CONCLUSIONS: The model included gestational age, neonatal respiratory distress syndrome, the levels of hemoglobin and creatine kinase-MB, gestational thyroid dysfunction, and Pa o2 had good prediction performance for predicting PPHN among newborns first admitted to the hospital after birth.
Asunto(s)
Nomogramas , Humanos , Recién Nacido , Femenino , Masculino , Curva ROC , Síndrome de Circulación Fetal Persistente/diagnóstico , Estudios Retrospectivos , Edad Gestacional , Hospitalización/estadística & datos numéricos , Modelos Logísticos , Síndrome de Dificultad Respiratoria del Recién Nacido/diagnóstico , Síndrome de Dificultad Respiratoria del Recién Nacido/epidemiologíaRESUMEN
We analyzed the relationship between recovery from coronary artery aneurysms (CAAs) and concurrent infections in patients with Kawasaki disease (KD). The estimated median time of aneurysm persistence between patients with and without infections was compared using Kaplan-Meier survival analyses. Risk factors associated with persistent CAAs at 2 years were identified using multivariable analyses. Co-infection was confirmed in 20.5% (106/518) of patients diagnosed with KD. No significant differences regarding treatment or coronary artery outcome were identified between patients with and without infections. The estimated median time of aneurysm persistence was higher in the co-infected group (9 vs. 6 months). A maximum Z-score ≥ 4.00 at 1 month had 78% sensitivity and 83% specificity in predicting CAAs without recovery within 1 year of onset, whereas the predictability was higher within 2 years of onset, with a Z-score ≥ 4.88 (sensitivity, 92%; specificity, 91%). Concomitant infections did not affect the response to treatment or coronary artery outcomes in patients with KD.
RESUMEN
Objectives: Kawasaki disease (KD) is a commonly acquired pediatric systemic vasculitis disease resulting in coronary artery aneurysm (CAA). The relationship between the ITPKC polymorphism (rs7251246) and the severity and susceptibility to KD in the Han Chinese population in Southern China remains unclear. Methods: We enrolled 262 children as controls and 221 children with KD (46 [20.8%] with intravenous immunoglobulin resistance and 82 [37.1%] with CAA). The relationship between the ITPKC rs7251246 polymorphism, KD susceptibility, and CAA formation was investigated. Results: While the ITPKC rs7251246 T>C polymorphism was not significantly associated with KD susceptibility, it was significantly related to the CAA risk in children with KD [CC/CT vs. TT: adjusted odds ratio [OR] 2.089, 95% confidence interval [CI] 1.085-4.020]. Male children with the rs7251246 CT/TT genotype had a significantly lower risk of thrombosis [CT/TT vs. CC: adjusted OR 0.251, 95% CI 0.068-0.923]. Children with KD, especially those with CAA, had significantly downregulated ITPKC mRNA compared to healthy children. ITPKC mRNA levels were lower in children with CAA who developed thrombosis (P=0.039). In children with KD, the CC genotype showed lower mRNA levels of ITPKC (P=0.035). Conclusion: The ITPKC rs7251246 T>C polymorphism may be a risk factor for CAA and thrombosis in children with KD in the Han Chinese population, likely due to differences in mature mRNA levels caused by interference of RNA splicing. Dual antiplatelet therapy for thrombosis is recommended for male children with the rs7251246 CC genotype.
Asunto(s)
Aneurisma Coronario , Síndrome Mucocutáneo Linfonodular , Fosfotransferasas (Aceptor de Grupo Alcohol) , Trombosis , Niño , Femenino , Humanos , Masculino , Aneurisma Coronario/complicaciones , Aneurisma Coronario/genética , Vasos Coronarios , Pueblos del Este de Asia , Predisposición Genética a la Enfermedad , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/genética , Polimorfismo de Nucleótido Simple , Trombosis/genética , Trombosis/complicaciones , Fosfotransferasas (Aceptor de Grupo Alcohol)/genéticaRESUMEN
INTRODUCTION: Multiple scoring systems for predicting intravenous immunoglobulin (IVIG) resistance have been developed. Although low-scoring patients with Kawasaki disease (KD) have a favorable prognosis, many develop coronary artery aneurysms (CAAs). Herein, we determined the risk factors for CAA development among patients with KD with low risk of IVIG resistance. METHODS: We compared 14 scoring systems for predicting IVIG resistance among patients with KD hospitalized from 2003 to 2022. Patients were risk stratified using an optimal scoring system. Association between baseline characteristics and CAA development was assessed within the low-risk group. RESULTS: Overall, 664 pediatric patients with KD were included; 108 (16.3%) had IVIG resistance, and the Liping scoring system had the highest area under the curve (0.714). According to this system, 444 (66.9%) patients with KD were classified as having low risk of developing IVIG resistance (<5 points). CAA development was significantly associated with male sex (odds ratio [OR], 1.946; 95% CI: 1.015-3.730), age <6 months at fever onset (OR, 3.142; 95% CI: 1.028-9.608), and a baseline maximum Z score of ≥2.72 (OR, 3.451; 95% CI: 2.582-4.612). CAA incidence increased with the number of risk factors, and comparisons with a Kobayashi score of <5 points among patients with KD revealed similar results. CONCLUSIONS: Predicting the response to IVIG might help further reduce CAA development in patients with KD.
Asunto(s)
Aneurisma Coronario , Enfermedad de la Arteria Coronaria , Síndrome Mucocutáneo Linfonodular , Niño , Humanos , Lactante , Masculino , Aneurisma Coronario/epidemiología , Aneurisma Coronario/etiología , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/complicaciones , Vasos Coronarios , Pueblos del Este de Asia , Inmunoglobulinas Intravenosas/uso terapéutico , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Síndrome Mucocutáneo Linfonodular/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Resistencia a Medicamentos , Medición de RiesgoRESUMEN
Objectives: The prognostic nutritional index (PNI) is a purported predictor of intravenous immunoglobulin (IVIG) resistance and coronary artery aneurysm (CAA) development in patients with Kawasaki disease (KD). However, limited data exist on CAA regression. This study aimed to confirm whether the PNI is a predictor for CAA persistency in patients with KD. Methods: This retrospective study grouped 341 patients with KD based on the coronary artery status and time of aneurysm persistence. The clinical and laboratory parameters were compared, and multivariate logistic regression analysis was performed to identify the independent risk factors for persistent CAA. The receiver operating characteristic (ROC) curve was further used to assess the predictive values of the PNI in persistent CAA. Results: Among the study patients, 80 (23.5%) presented with CAA, including CAA persisting for 2 years in 17 patients (5.0%). Patients with CAA were more frequently treated with corticosteroids (p < 0.016). No statistically significant differences were found in the nutritional status and PNI among patients with or without coronary artery lesions, regardless of injury severity. Patients in the persistent CAA group presented with higher rates of overnutrition and showed lower PNI values and a higher incidence of thrombosis than those in the normal group (p < 0.05). The PNI and the maximum Z-score at 1 month of onset were significantly associated with CAA persisting for 2 years and may be used as predictors of persistent CAA. The area under the ROC curve was 0.708 (95% confidence interval, 0.569-0.847), and a 40.2 PNI cutoff yielded a sensitivity and specificity of 41 and 92%, respectively, for predicting CAA persisting for 2 years. Kaplan-Meier survival analysis revealed that the estimated median time of aneurysm persistence was significantly higher in patients with PNI values of ≤40 than in those with PNI values of >40 (hazard ratio, 2.958; 95% confidence interval, 1.601-5.464; p = 0.007). After sampling-time stratification, the PNI differed significantly between patients with and without persistent CAA when sampled on the second (p = 0.040), third (p = 0.028), and fourth days (p = 0.041) following disease onset. Conclusion: A lower PNI value is an independent risk factor for CAA persisting for 2 years in patients with KD, besides the maximum Z-score at 1 month after onset. Furthermore, the PNI obtained within 4 days from fever onset may possess greater predictive power for patients with persistent CAA.
RESUMEN
We herein report two cases involving children who died of influenza A (H3N2) virus infection-associated encephalopathy/encephalitis (IAE). Both children developed convulsions and impaired consciousness within a relatively short period and eventually died of brainstem failure. Patient 1 presented with high fever, vomiting, and diarrhea. Laboratory tests indicated persistently high lactate, alanine aminotransferase, and urea nitrogen concentrations in the blood as well as a high protein concentration in the cerebrospinal fluid. Patient 2 presented with persistent hyperthermia and progressive disturbance of consciousness, but the cerebrospinal fluid remained normal during the disease course. Both patients were actively given oseltamivir antiviral treatment after diagnosis of influenza virus infection. However, the disease progressed and invasive mechanical ventilation was performed. Both children's condition quickly progressed to IAE, and they eventually died. IAE is a rare complication of influenza virus infection with high mortality, and its pathogenesis remains unclear. The purpose of this report is to draw attention to the serious central nervous system complications of influenza infection and raise awareness of the fatal consequences of this disease among pediatricians.
Asunto(s)
Encefalopatías , Encefalitis , Gripe Humana , Infecciones por Orthomyxoviridae , Humanos , Niño , Gripe Humana/diagnóstico , Subtipo H3N2 del Virus de la Influenza A , Encefalopatías/complicaciones , Encefalopatías/diagnóstico , Oseltamivir/uso terapéuticoRESUMEN
OBJECTIVES: We aimed to evaluate the clinical and laboratory characteristics of patients with Kawasaki disease (KD) before and after therapy. METHODS: Patients with KD were divided into different groups according to their responsiveness to initial intravenous immunoglobulin (IVIG) treatment and coronary status. The clinical and laboratory parameters before and after therapy were compared. Multivariate analysis was performed to identify the independent risk factors, and the receiver operating characteristic (ROC) curve was applied to assess and compare the prediction ability of risk factors and their fluctuations. RESULTS: Of the 153 patients included in the study, 41 (26.8%) had IVIG resistance and 37 (24.2%) had developed CAA. After stratifying by therapy response, the two groups differed in the levels of total bilirubin (TSB), albumin, and sodium, neutrophil-to-lymphocyte count ratio (NLR), platelet-to-lymphocyte count ratio (PLR), TSB-to-albumin (B/A) ratio, and prognostic nutritional index (PNI) before IVIG, and in the white blood cell count (WBC), neutrophil count, levels of hemoglobin, C-reactive protein (CRP), alanine aminotransferase (ALT), and albumin, NLR, PNI, capillary leakage index (CLI), and systemic immune-inflammation index (SII) after IVIG. Multivariate analysis revealed that the B/A ratio before IVIG and CLI and SII after IVIG were significantly and positively associated with IVIG resistance and that there was a larger decline in the B/A ratio and smaller decline in CLI and SII pre- and post-treatment in the IVIG-resistant group than in the IVIG-responsive group. However, no statistical differences in the fluctuations of the B/A ratio, CLI, and SII as well as all parameters before and after therapy were observed in patients with and without CAA. ROC curve analyses found a greater AUC value of post-treatment parameters (0.751 and 0.706 for CLI and SII, respectively) compared with pre-treatment parameters (0.654 for B/A ratio) in predicting IVIG resistance; however, the predictive ability of the fluctuations in risk factors before and after therapy was not superior to that of baseline values. CONCLUSIONS: The B/A ratio before IVIG and CLI and SII after IVIG were risk factors for IVIG resistance in patients with KD, independent of CAA development. Key Points ⢠A high total bilirubin-to-albumin ratio before IVIG and high capillary leakage and systemic immune-inflammation indices after IVIG may indicate an increased risk of intravenous immunoglobulin resistance in patients with Kawasaki disease. ⢠Post-treatment parameters were superior to pre-treatment parameters in terms of prediction; therefore, rapid and repeated assessment of risk factors before and after treatment must be considered in children in whom the vital signs and symptoms do not improve after treatment.
Asunto(s)
Aneurisma Coronario , Enfermedad de la Arteria Coronaria , Síndrome Mucocutáneo Linfonodular , Niño , Humanos , Inmunoglobulinas Intravenosas , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Síndrome Mucocutáneo Linfonodular/diagnóstico , Vasos Coronarios , Inflamación/complicaciones , Aneurisma Coronario/complicaciones , Proteína C-Reactiva/análisis , Estudios Retrospectivos , Enfermedad de la Arteria Coronaria/complicacionesRESUMEN
Importance: Patients with Kawasaki disease (KD) experience various extracardiovascular injury complications, which may affect their outcomes. Objective: To investigate the incidence and clinical characteristics of extracardiovascular complications in children with KD. Methods: The clinical data of patients diagnosed with KD in the First Affiliated Hospital of Guangxi Medical University from January 2003 to January 2021 were reviewed. The clinical characteristics and extracardiovascular complications were compared among patients stratified by age, intravenous immunoglobulin (IVIG) therapy responsiveness, and coronary status. Results: A total of 511 patients with KD were included, 357 (69.9%) were aged 1-5 years. Children aged <1 year (21.5%) and boys (70.8%) were more likely to have coronary artery lesions (CALs). The incidence of incomplete KD was lowest in 1-5-year-old patients (19.6%). Involvement of the hematological system gradually decreased with age (<1 year, 51.8%; 1-5 years, 36.7%; >5 years, 29.5%), whereas the involvement of the joints gradually increased with age (<1 year, 2.7%; 1-5 years, 6.2%; >5 years, 20.5%). Nervous system involvement was more common in IVIG non-responders (15.7% [13/83] vs. 5.4% [23/428], P = 0.001). However, there were no significant differences in extracardiovascular injury complications between patients with or without CALs. Interpretation: KD can involve multiple organ injuries as well as cardiovascular complications, and nervous systerm involvement may be more common in patients unresponsive to IVIG.
RESUMEN
Coronary artery aneurysm (CAA) is a serious cardiac complication arising from Kawasaki disease (KD) and is becoming the leading cause of acquired heart disease in children. The aim of this study was to determine the potential risk factors associated with coronary artery aneurysms (CAAs), which differ in size and emergence time, and track its regression within 3 years of onset. The laboratory data, clinical features, and coronary artery outcomes of patients, who were diagnosed with KD and received treatment from January 2003 to January 2019 were retrospectively analyzed. A total of 484 pediatric patients with KD were examined during the study period. Among them, 130 (26.9%) presented with CAA, including mid- to large-sized CAA in 38 patients (7.9%) and de novo CAA after intravenous immunoglobulin (IVIG) treatment in 22 patients (4.5%). Albumin-to-globin (A/G) ratio was significantly negatively associated with the absolute internal diameter of coronary artery at 1 month of onset and may be used as a predictor of mid- to large-sized CAA development in patients with KD. The area under the receiver operating characteristic curve was 0.637 (95% confidence interval: 0.551-0.724), and a cutoff of 1.32 yielded a sensitivity and specificity of 79 and 49%, respectively, for predicting mid- to large-sized CAA development. De novo CAA after IVIG may lead to an increased risk of developing progressive CAA [13 (59.1%) of 22 vs. 31 (28.7%) of 108; P = 0.006] and had significantly greater changes in both the magnitude of CAA dimension variation and maximum z-score of the coronary arteries at 2 and 4 weeks and then 3 months after onset (P < 0.001). Kaplan-Meier survival analysis revealed that the estimated median time of aneurysm persistence was significantly higher in the progressive CAA group than in the non-progressive CAA group (25 vs. 4 months, P < 0.001), as well as among the three groups of patients (giant CAA > medium-sized CAA > small-sized CAA, P < 0.001). Children with KD who had low A/G ratio were more likely to develop mid- to large-sized CAA. Nevertheless, de novo CAA after IVIG treatment may increase the risk of more severe arterial damage and development of progressive coronary artery damage; and both mid- to large-sized and de novo CAA could dramatically prolong coronary artery normalization time. Thus, aggressive risk modifications should be employed, and close monitoring with frequent echocardiography is needed for this vulnerable patient population.
RESUMEN
Background: Circular RNAs (circRNAs) may play important roles in the progression of pulmonary arterial hypertension. However, the potential roles they play in childhood pulmonary arterial hypertension associated congenital heart disease (CHD) progression remains unclear. Methods: Thirteen human plasma samples including eight from pulmonary arterial hypertension secondary to CHD patients and five from a control group were analyzed using the Arraystar Human circRNA array. The relative expression levels of five differentially expressed circRNAs in pulmonary arterial hypertension were detected using real-time polymerase chain reaction (PCR) analysis. In parallel, these levels were also taken on control samples from 32 CHD patients. We used miRanda and TargetScan software packages to predict potential microRNA (miRNA)targets, which were then combined into a circRNA-miRNA-messenger RNA (mRNA) network. Results: Twenty-seven circRNAs (three upregulated and 24 downregulated) were differentially expressed between the pulmonary arterial hypertension and control groups. Compared to control group levels, circ_003416 expression in the pulmonary arterial hypertension group was significantly downregulated, while circ_005372 expression, in contrast, was significantly upregulated. The differential expression of these circRNAs was mainly linked to variation in levels of oxidative phosphorylation and tight junction signaling. Conclusions: We identified one overexpressed and one underexpressed circRNA in plasma samples from children with CHD associated pulmonary arterial hypertension. Bioinformatic analysis indicated these dysregulated circRNAs might be associated with the occurrence and regulation of pulmonary arterial hypertension.
RESUMEN
INTRODUCTION: Proliferation and apoptosis of pulmonary artery smooth muscle cells (PASMCs) play an important role in the occurrence and development of pulmonary arterial hypertension (PAH). The purpose of this study was to investigate the effects of survivin inhibitor YM155 on the proliferation and apoptosis of PASMCs in rats with PAH induced by high pulmonary blood flow. METHODS: Thirty male Sprague-Dawley (SD) rats were randomly divided into control, model, and YM155 intervention groups. A rat model of PAH induced by high pulmonary blood flow was established, and it was confirmed by assessments of right-ventricular pressure (RVP) and right ventricular hypertrophy index (RVHI). Immunohistochemical staining and western blot analysis were used to detect the expression of survivin, and the proliferation and apoptosis of PASMCs. Lastly, the effects of in vivo treatment of YM155 were tested. RESULTS: The increased expression of survivin mRNA and protein were observed in the model group, accompanied by pulmonary arteriolar wall thickening, lumen stenosis, and perivascular inflammatory cell infiltration. Elevated expression of survivin and pulmonary vascular remodeling were significantly mitigated after YM155 treatment. Specifically, the YM155 intervention group had a significantly lower PASMC proliferation rate and a higher PASMC apoptotic rate. CONCLUSION: YM155 suppressed PASMC proliferation and promoted PASMC apoptosis by inhibiting survivin expression and thereby reducing pulmonary vascular remodeling in high pulmonary blood flow-induced PAH in vivo.
Asunto(s)
Hipertensión Arterial Pulmonar , Arteria Pulmonar , Animales , Apoptosis , Proliferación Celular , Masculino , Músculo Liso Vascular , Miocitos del Músculo Liso/metabolismo , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Circulación Pulmonar , Ratas , Ratas Sprague-Dawley , Survivin/metabolismo , Survivin/farmacología , Remodelación VascularRESUMEN
Background: The factors predicting high-risk Kawasaki disease (KD) remain unclear. Therefore, we aimed to determine the risk factors for resistance to intravenous immunoglobulin (IVIG) treatment and coronary artery aneurysm (CAA) development in a Chinese pediatric population with high-risk KD. Methods: We compared the performances of 11 scoring systems that have been reported to predict IVIG resistance among patients with KD hospitalized from January 2013 through August 2021. Patients were risk-stratified based on the optimal scoring system. The association of baseline characteristics with IVIG treatment resistance and CAA development was investigated within the high-risk group of KD. Results: In total, 346 pediatric patients with KD were included, of whom 63 (18.2%) presented with IVIG resistance. The Kobayashi score and five Chinese scoring system scores (Tang et al., Yang et al., Lan et al., Liping et al., and Wu et al.) were significantly higher in the IVIG non-responsive KD group than in the IVIG responsive KD group, and the results of the receiver operating characteristic (ROC) curves analysis were observed to be highest in the Xie Liping scoring system for IVIG resistance (area under the curve, 0.650). Especially, 87 (25.1%) patients comprised the high-risk KD group based on this optimal scoring system (≥5 points). IVIG resistance was significantly associated with the total bilirubin-to-albumin ratio (B/A ratio) [odds ratio, 7.427; 95% confidence interval (CI): 1.022-53.951]. The area under the ROC was 0.703 (95% CI: 0.586-0.821), and the cutoff point was 0.383, which indicated a sensitivity and specificity for predicting treatment resistance of 58% and 80%, respectively. The serum albumin level (odds ratio, 1.401; 95% CI: 1.049-1.869) and Z score of the left main coronary artery (odds ratio, 9.023; 95% CI: 1.070-76.112) were independent predictors of CAA development. Conclusions: In the Chinese pediatric population with KD, the Xie Liping scoring system is the most appropriate method for identifying high-risk patients, and IVIG resistance could be predicted based on the B/A ratio. Serum albumin level and Z score of the left main coronary artery at baseline were warning indicators for CAA development. More intensified or adjunctive therapies and close follow-up should be considered for high-risk patients with these risk factors.
RESUMEN
BACKGROUND: Circular RNAs (circRNAs) have been found to be involved in the development of pulmonary arterial hypertension (PAH). However, their diagnostic value in pediatric PAH remains unclear. This study aimed to examine the characteristic expression of the circRNA hsa_circ_0003416 in the plasma of children with PAH caused by congenital heart disease (CHD); the potential of hsa_circ_0003416 as a diagnostic biomarker was also investigated. METHODS: The plasma expression levels of hsa_circ_0003416 were determined via quantitative reverse transcription-polymerase chain reaction in 50 CHD patients, 50 PAH patients, and 20 healthy subjects; the associations between hsa_circ_0003416 levels and clinical data were analyzed thereafter. Receiver operating characteristic curves were employed to determine the diagnostic capacity of this circRNA. RESULTS: Expression levels of hsa_circ_0003416 in plasma were lower in the PAH-CHD group than in the CHD and healthy control groups (p = 0.009 vs. healthy control group, p = 0.026 vs. CHD group). Moreover, hsa_circ_0003416 was found to be negatively associated with B-type natriuretic peptide (r = -0.342, p = 0.013). In addition, the area under the curve of hsa_circ_0003416 levels in plasma was 0.721 (95% confidence intervals = 0.585-0.857, p = 0.004), suggesting that it has a promising diagnostic value. CONCLUSIONS: Overall, hsa_circ_0003416 was found to be significantly downregulated in children with PAH-CHD and to be potent as a biomarker for PAH-CHD diagnosis.
Asunto(s)
Cardiopatías Congénitas , Hipertensión Arterial Pulmonar , Biomarcadores , Niño , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/genética , Humanos , ARN , ARN Circular/genética , Curva ROCRESUMEN
Pulmonary arterial hypertension (PAH) is a complex devastating disease relevant to remarkable metabolic dysregulation. Although various research studies on PAH from a metabolic perspective have been emerging, pathogenesis of PAH varies in different categories. Research on metabolic reprogramming in flow-associated PAH remains insufficient. An untargeted metabolomic profiling platform was used to evaluate the metabolic profile of pulmonary arteries (PAs) as well as the right ventricle (RV) in a flow-associated PAH rat model in the present work. A total of 79 PAs and 128 RV metabolites were significantly altered in PAH rats, among which 39 metabolites were assessed as shared dysregulated metabolites in PAs and the RV. Pathway analysis elucidated that, in PAs of PAH rats, pathways of phenylalanine, tyrosine, and tryptophan biosynthesis and linoleic acid metabolism were significantly altered, while in the RV, arginine biosynthesis and linoleic acid metabolism were altered dramatically. Further integrated analysis of shared dysregulated PA and RV metabolites demonstrated that the linoleic acid metabolism and the arachidonic acid (AA) metabolism were the key pathways involved in the pathogenesis of flow-associated PAH. Results obtained from the present work indicate that the PAH pathogenesis could be mediated by widespread metabolic reprogramming. In particular, the dysregulation of AA metabolism may considerably contribute to the development of high blood flow-associated PAH.
RESUMEN
We evaluated the combined effect of obesity and family history (FH) on the risk of hypertension in adolescents. We studied 1288 school-aged adolescents aged 16.0 ± 0.5 years (49.0% males) attending the medical examination for enrollment in the city of Nanning, China. Their blood pressure, weight, and height were measured. A questionnaire was administered to both adolescents and their parents to obtain information on the participants' medical history. Multiple logistic regression analysis, according to bodyweight categories and adjusted for age, gender, and body mass index (BMI), was done to determine the association of FH with hypertension. Hypertension was found in 14.1% of adolescents. The prevalence of hypertension was significantly higher in adolescents with obesity and positive FH than their normal weight and negative FH counterparts. For adolescents with normal weight and waist circumstance (WC), those with a positive FH in parents compared to those without had an significantly increased risk for hypertension (odds ratio [OR], 2.15; 95% confidence interval [CI] 1.28-3.61, and 1.96; 95% CI 1.16-3.32, respectively). These findings were adjusted for age, gender, and BMI. Our study showed that routine screening for pediatric hypertension should be performed in adolescents who are overweight and obese. Furthermore, parental FH of hypertension played an important role in predicting the hypertension phenotype among adolescents with normal weight.
Asunto(s)
Hipertensión , Adolescente , Índice de Masa Corporal , Niño , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Obesidad/epidemiología , Obesidad/genética , Sobrepeso , Prevalencia , Factores de RiesgoRESUMEN
Objective: The aim of this study was to investigate the clinical characteristics and factors associated with pediatric hypertension and target organ damage (TOD). Methods: We retrospectively reviewed clinical data from 205 children with hypertension treated in our hospital from 2007 to 2018. The patients were classified based on the type of hypertension (primary, secondary) and presence of TOD (heart, brain, retina). Logistic regression analysis was performed to identify the factors independently associated with hypertension and TOD. Results: There were 107 males, 97 females, and one intersex in this study, with an age range of 0.1-17.9 years. Majority of cases (177, 86.3%) had secondary hypertension, while 13.7% had primary hypertension. The most frequent cause of secondary hypertension was renal disease (59.32%). Elevated serum creatinine level (odds ratio [OR] = 7.22, 95% confidence interval [95% CI] = 1.6-32.62, P = 0.01), blood urea nitrogen (OR = 6.33, 95% CI = 1.81-22.19, P = 0.004), serum uric acid level (OR = 3.66, 95% CI = 1.20-11.22, P = 0.023), and albuminuria (OR = 3.72, 95% CI = 1.50-9.26, P = 0.005) were independently associated with secondary hypertension. Elevated serum uric acid and blood urea nitrogen levels were associated with left ventricular hypertrophy (OR = 6.638, 95% CI = 1.349-32.657, P = 0.02) and hypertensive encephalopathy (OR = 4.384, 95% CI = 1.148-16.746, P = 0.031), respectively. Triglyceride level correlated with hypertensive retinopathy (P = 0.001). Conclusion: Pediatric hypertension was most often secondary, with renal disease as the leading cause. Elevated levels of serum uric acid, blood urea nitrogen, serum creatinine, and albuminuria may indicate secondary hypertension in childhood. Elevated serum uric acid, blood urea nitrogen, and triglyceride levels were associated with left ventricular hypertrophy, hypertensive encephalopathy, and hypertensive retinopathy, respectively.
RESUMEN
Background: Unhealthy dietary and lifestyle behaviors are associated with a higher prevalence of non-communicable chronic diseases and higher mortality in adults. However, there remains some uncertainty about the magnitude of the associations between lifestyle behaviors and cardiovascular factors in adolescents. Methods: We conducted a school-based cross-sectional study of 895 Chinese adolescents aged 15-19 years. They participated in a questionnaire survey, physical examination, and blood sample collection. Latent class analysis (LCA) was used to identify heterogeneous subgroups of lifestyle behaviors. A set of 12 latent class indicators, which reflected lifestyle behaviors including dietary habits, physical activity, sleep duration, screen time, and pressure perception, were included in the analysis. Logistic regression analysis was performed to determine whether the derived classes were related to a cardiometabolic risk. Results: In total, 13.7 and 5.6% of the participants were overweight and obese, respectively, and 8.4 and 14.1% reported having pre-hypertension and hypertension, respectively. A two-class model provided the best fit with a healthy lifestyle pattern (65.8%) and a sub-healthy lifestyle pattern (34.2%). There were more female participants with a healthy lifestyle (56.2 vs. 43.8%), whereas there were more males with a sub-healthy lifestyle (45.4 vs. 54.6%), (all P = 0.002). Increased risk of cardiometabolic abnormality (BMI categories, blood pressure and lipids) was not significant across lifestyle patterns, except for waist circumference (70.5 vs 69.1 cm, P = 0.044). There was no significant difference in physical activity and intake of fruit and vegetable between the two patterns. Conclusion: Primary prevention based on lifestyle modification should target patterns of behaviors at high risk in adolescents. Due to the complex effect of lifestyle clusters on cardiometabolic risks, well-designed and prospective studies in adolescents are needed in the future.